Immune pathways for translating viral infection into chronic airway disease. Adv Immunol 2009;102:245-76
Date
05/30/2009Pubmed ID
19477323Pubmed Central ID
PMC3010226DOI
10.1016/S0065-2776(09)01205-XScopus ID
2-s2.0-66049132845 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
To better understand the immune basis for chronic inflammatory lung disease, we analyzed a mouse model of lung disease that develops after respiratory viral infection. The disease that develops in this model is similar to asthma and chronic obstructive pulmonary disease (COPD) in humans and is manifested after the inciting virus has been cleared to trace levels. The model thereby mimics the relationship of paramyxoviral infection to the development of childhood asthma in humans. When the acute lung disease appears in this model (at 3 weeks after viral inoculation), it depends on an immune axis that is initiated by expression and activation of the high-affinity IgE receptor (FcvarepsilonRI) on conventional lung dendritic cells (cDCs) to recruit interleukin (IL)-13-producing CD4(+) T cells to the lower airways. However, when the chronic lung disease develops fully (at 7 weeks after inoculation), it is driven instead by an innate immune axis that relies on invariant natural killer T (iNKT) cells that are programmed to activate macrophages to produce IL-13. The interaction between iNKT cells and macrophages depends on contact between the semi-invariant Valpha14Jalpha18-TCR on lung iNKT cells and the oligomorphic MHC-like protein CD1d on macrophages as well as NKT cell production of IL-13 that binds to the IL-13 receptor (IL-13R) on the macrophage. This innate immune axis is also activated in the lungs of humans with severe asthma or COPD based on detection of increased numbers of iNKT cells and alternatively activated IL-13-producing macrophages in the lung. Together, the findings identify an adaptive immune response that mediates acute disease and an innate immune response that drives chronic inflammatory lung disease in experimental and clinical settings.
Author List
Holtzman MJ, Byers DE, Benoit LA, Battaile JT, You Y, Agapov E, Park C, Grayson MH, Kim EY, Patel ACMESH terms used to index this publication - Major topics in bold
AnimalsCD4-Positive T-Lymphocytes
Chemokines, CC
Chronic Disease
Complement Pathway, Alternative
Dendritic Cells
Humans
Interleukin-13
Lung Diseases
Macrophages
Natural Killer T-Cells
Receptors, IgE
Virus Diseases
